Enhanced Cancer Immunotherapy with Smad3-Silenced NK-92 Cells
Publication in refereed journal

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其它資訊
摘要Natural killer (NK) cells, early effectors in anti-cancer immunity, are paralyzed by TGF-β1, an immunosuppressive cytokine produced by cancer cells. Development and activity of NK cells are largely inhibited in the Smad3-dependent tumor microenvironment. Here, we used genetic engineering to generate a stable SMAD3-silencing human NK cell line NK-92-S3KD, whose cancer-killing activity and cytokine production were significantly enhanced under TGF-β1-rich condition compared to the parental cell line. Interestingly, we identified that IFNG gene is a direct E4BP4 target gene. Thus, silencing of SMAD3 allows up-regulation of E4BP4 that subsequently promoting interferon-gamma (IFN-gamma) production in the NK-92-S3KD cells. More importantly, NK-92-S3KD immunotherapy increases the production of not only IFN-gamma, but also granzyme B and perforin in tumor; therefore inhibiting cancer progression in two xenograft mouse models with human hepatoma (HepG2) and melanoma (A375). Thus, the NK-92-S3KD cell line may be useful for clinical immunotherapy of cancer.
出版社接受日期12.06.2018
著者Qing-Ming Wang, Patrick Ming-Kuen Tang, Guang-Yu Lian, Chunjie Li, Jinghong Li, Xiao-Ru Huang, Ka-Fai To, Hui-Yao Lan
期刊名稱Cancer Immunology Research
出版年份2018
月份8
卷號6
期次8
出版社American Association for Cancer Research
頁次965 - 977
國際標準期刊號2326-6066
電子國際標準期刊號2326-6074
語言英式英語

上次更新時間 2020-06-08 於 04:26